Superoxide Dismutase-Overexpressing Mice Are Resistant to Ozone-Induced Tissue Injury and Increases in Nitric Oxide and Tumor Necrosis Factor-α

Ladan Fakhrzadeh, Jeffrey D. Laskin, Carol R. Gardner, Debra L. Laskin

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Reactive oxygen intermediates have been implicated in lung injury induced by inhaled irritants. The present studies used mice overexpressing Cu/Zn-superoxide dismutase (SOD+/+) to analyze their role in ozone-induced lung inflammation and cytotoxicity. Treatment of wild-type mice with ozone (0.8 ppm, 3 h) resulted in increased bronchoalveolar lavage fluid protein, which was maximal after 24-48 h. Significant increases in lung macrophages and 4-hydroxyalkenals were also observed. In contrast, bronchoalveolar lavage fluid protein and macrophage content and 4-hydroxyalkenals were at control levels in ozone-treated SOD+/+ mice. There was also no evidence of peroxynitrite-mediated lung damage, demonstrating that SOD+/+ mice are resistant to ozone toxicity. Whereas alveolar macrophages from wild-type mice produced increased amounts of nitric oxide and expressed more inducible nitric oxide synthase, phospholipase A2, and tumor necrosis factor-α after ozone inhalation, this was not evident in cells from SOD+/+ mice. Ozone-induced decreases in interleukin-10 were also not observed. In wild-type mice, ozone inhalation resulted In activation of nuclear factor-κB, which regulates proinflammatory gene activity. This response was significantly reduced in SOD+/ + mice. These data demonstrate that antioxidant enzymes play a critical role in ozone-induced tissue injury and in inflammatory mediator production.

Original languageEnglish (US)
Pages (from-to)280-287
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume30
Issue number3
DOIs
StatePublished - Mar 2004

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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